The objective of the proposed research is the control of acute rheumatic fever (ARF) and acute glomerulonephritis (AGN) by: (a) the production of a successful vaccine, (b) increased understanding of the epidemiologic factors that cause streptococcal sequels, and (c) further understanding of the specific pathogenesis of these sequels. The differences in the epidemiology, bacteriology and immunology of the antecedent Group A streptococcal infections that cause ARF and AGN, respectively, are the focus of our studies so that we may determine more precisely the differences between strains that seem to cause one sequel or the other, but apparently not both. Detailed studies and comparisons of the antigenic composition and biologic properties of such "rheumatogenic" and "nephritogenic" strains are in progress. Vaccines prepared from purified fractions of streptococcal M protein continue to be analyzed to determine whether or not their toxic properties in human and animal hosts can be reduced, whether they contain cross reacting antigens with host tissues that may result in serious reactions, or, indeed, whether they may be involved in the pathogenesis of either or both sequels. Comparisons between "rheumatogenic" and "nephritogenic" M proteins and protoplast membranes for antigenic cross reactivity with the heart and kidney tissue components are in progress with particular emphasis upon cellular hyperimmune reactions (delayed allergy) to streptococcal products.